F036-Controversies in Vitamin D VITAMIN D AND ATOPIC DERMATITIS Tissa Hata M.D. Professor, UCSD Department of Dermatology
DISCLOSURE OF RELATIONSHIPS WITH INDUSTRY Tissa Hata M.D. F036-Controversies in Vitamin D DISCLOSURES GlaxoSmithKline-Investigator-Grants Galderma-Investigator-Grants Janssen-Investigator-Grants Abbvie-Advisory Board-Honoraria Bristol Myers Squibb-Investigator-Grants
ABNORMAL BARRIER IN ATOPIC DERMATITIS Altered lipid composition with decreased ceramides Decreased hydration with increased TEWL Decreased fillaggrin Normal skin Atopic Skin Clinics in Dermatology (2017) 35, 349 353
HBD-2 (µm in epidermis) LL-37 (µm in epidermis) Ong PY, Ohtake T, Brandt C, Strickland I, Boguniewicz M, Ganz T, Gallo RL, Leung DY. (2002) N Engl J Med 347:1151-60 Decreased expression of antimicrobial peptides in Atopics 3000 b-defensin (HBD-2) 3000 Cath (LL-37) 2000 2000 1000 1000 0 0 AD Psoriasis AD Psoriasis
Could Vitamin D be the answer to Atopic dermatitis?
Vitamin D polymorphisms and Atopic Dermatitis A rare variant in CYP27A1 and its association with atopic dermatitis with high serum total IgE. Suzuki H, Makino Y, Nagata M, Furuta J, Enomoto H, Hirota T, Tamari M, Noguchi E. Allergy. 2016 Oct;71(10):1486-9. Vitamin D Receptor Gene BSMI, FOKI, APAI, and TAQI Polymorphisms and the Risk of Atopic Dermatitis. Kılıç S, Sılan F, Hız MM, Işık S, Ögretmen Z, Özdemir Ö. J Investig Allergol Clin Immunol. 2016;26(2):106-10 A Promoter Polymorphism of the Vitamin D Metabolism Gene Cyp24a1 is Associated with Severe Atopic Dermatitis in Adults.Hallau J, Hamann L, Schumann RR, Worm M, Heine G. Acta Derm Venereol. 2016 Feb;96(2):169-72 Association of vitamin D receptor gene polymorphisms with severe atopic dermatitis in adults. Heine G, Hoefer N, Franke A, Nöthling U, Schumann RR, Hamann L, Worm M. Br J Dermatol. 2013 Apr;168(4):855-8
Vitamin D has many functions! Muehleisen B1, Gallo RL. Vitamin D in allergic disease: shedding light on a complex problem. J Allergy Clin Immunol. 2013 Feb;131(2):324-9. doi: 10.1016/j.jaci.2012.12.1562.
Vitamin D Functions for the Barrier Functions in skin barrier Promotes keratinocyte differentiation Increases synthesis of barrier proteins involucrin,transglutaminase, loricrin and filaggrin Increases lipid content of barrier by processing of long chain glycosylceramides and transport into lamellar bodies Skin Pharmacol Physiol 2018;31:74 86
VDRE found in the promotor of cathelicidin gene (CAMP) Addition of 1,25(OH)2D3 to human keratinocytes induces cathelicidin production
Vitamin D does possess many functions beneficial to our AD patients Are lower levels of vitamin D associated with AD or AD severity?
Study No. of subjects 25 OHD and AD 25 OHD and AD severity Peroni DG. Br J Dermatol. 2011 May;164(5):1078-82 37 children with AD, Verona Italy Yes Kanda N. Allergy. 2012 Jun;67(6):804-26 patients with 12 AD and 27 age matched controls in Japan YES Akan A. Pediatr Dermatol. 2013 May- Jun;30(3):359-63 73 children with AD +/- sensitization Ankara Turkey Yes with + sensitization No with - sensitization Samochoki Z. J. Am. Acad. Dermatol. 2013, 69, 238 244. 95 Adults age 18-50 with AD, 58 control in Poland No No Chiu YE. J Am Acad Dermatol. 2013 Jul;69(1):40-6 97 subjects with AD age 1-18 from Wisconsin Dermatology No El Taieb. Dermatitis. 2013 Nov- Dec;24(6):296-301 29 patient with AD between 2-12 and 30 controls from Egypt Yes Yes Wang SS. Pediatr Allergy Immunol. 2014 Feb;25(1):30-5 487 AD children and 328 non allergic controls from Hong Kong Yes Yes Cheng HM. J Allergy Clin Immunol. 2014 Apr;133(4) 15,212 adults 19 years or older, 392 with AD Korea Yes DiFilippo P. Int Arch Allergy Immunol. 2015;166(2):91-6 39 children with AD and 20 controls in Chieti Italy No
Study No. of subjects 25OHD and AD 25OHD and AD severity Baek J. J Pediatr. 2014 Oct;165(4):849-54 168 infants with atopic dermatitis, Korea Yes Noh S. J Allergy Clin Immunol. 2014 Jun;133(6):1767-70.e6. 82 subjects with AD, 49 control in Korea No Cheon BR. Korean J Pediatr. 2015 Mar;58(3):96-101 91 children with AD and 32 control in Korea Yes Yes Barman M. Acta Paediatr. 2015 Apr;104(4):405-13. 13 year olds, 55 with AD and 55 healthy in Sweden No Han TY, Ann Dermatol. 2015 Feb;27(1):10-4 Thuesen BH, Allergy. 2015 Nov;70(11):1501-1504 72 (39 adults and 33 children)with AD and 140 healthy in Korea 2308 adult participants, mean age 49, 230 with AD in Denmark Yes in children No in adults No Robl, Pediatr Dermatol 2016 May;33(3):283-8 105 children younger than 14 years with AD in Brazil No Berents TL Br J Dermatol. 2016 Jul;175(1):95-101 170 children with AD in Norway, mean age 5.1 months, 240 healthy in Norway Byun EJ BMJ Open. 2017 Jul 10;7(7):e016409 2515 between 10-18 years, 250 with AD in Korea No No
7 observational studies (906 AD patients vs 657 controls)
Kim MJ1, Kim SN2, Lee YW3,4, Choe YB5,6, Ahn KJ. Vitamin D Status and Efficacy of Vitamin D Supplementation in Atopic Dermatitis: A Systematic Review and Meta-Analysis. Nutrients. 2016 Dec 3;8(12).
Kim MJ1, Kim SN2, Lee YW3,4, Choe YB5,6, Ahn KJ. Vitamin D Status and Efficacy of Vitamin D Supplementation in Atopic Dermatitis: A Systematic Review and Meta-Analysis. Nutrients. 2016 Dec 3;8(12).
Kim MJ1, Kim SN2, Lee YW3,4, Choe YB5,6, Ahn KJ. Vitamin D Status and Efficacy of Vitamin D Supplementation in Atopic Dermatitis: A Systematic Review and Meta-Analysis. Nutrients. 2016 Dec 3;8(12).
Database from 1966-2015 for Randomized Controlled Trials
Study Study design Amestejani 2012[3] RCT Di Filippo, 2015[13] CT Byremo 2006[9] RCT Camargo 2014[20] RCT Hata 2014[21] RCT Javanbakht, 2011[22] RCT Norizoe, 2014[23] RCT No. of subjects vs. control Mean age of subjects (±SD) 30 vs. 30 23.34 ± 2.1 39 vs. 20 4 ± 3.15 32 vs. 29 7.88 (range 3 13) 58 vs. 49 9 ± 5 30 vs. 30 31.6 ± 10.67 13 vs. 13 23.7 ± 2.43 82 vs 82 31.0 ± 5.13 Intervention type duration source Main outcome 1600 IU Cholecalciferol 8 wk, Oral SCORAD Mean change[experimental, control] [ 9.5 ± 3.7, 1.8 ± 4.8] P value 1000 IU cholecalciferol 2 wkoral SCORAD -23.56 ± 15.48, NR <0.001 Sun exposure in Canary Islands [ 16.0 ± 18.5, verses Norway SCORAD 6.2 ± 17.4] <0.0005 1000 IUCholecalciferol 4 wk Oral EASI 4000 IU Cholecalciferol 3 wk Oral 25(OH)D3 1600 IUCholecalciferol 8 wk Oral SCORAD 0.01 [ 6.5 ± 8.8 3.3 ± 7.6] 0.04 [9.4 ± 11.23, 9.4 ± 12.43] <0.01 12.7 ± 11.6 9.4 ± 10.9 NR 800 IU Cholecalciferol 6 wkoral SCORAD 4.75 ± 7.49, 3.95 ± 5.36 0.62 Sidbury, 2008[08] RCT Hata 2008[12] CT 5 vs. 6 1000 IU median 7 (range 2 13) Ergocalciferol 4 wk, Oral EASI [ 4.6 ± NR, 2.2 ± NR] 0.4 14 vs. 14 NR 4000 IUCholecalciferol 3 wk, Oral Cathelicidin [20.38 RCU, 0.78 RCU] <0.01
Supplementation shows a statistically significant decrease in severity of AD symptoms
Supplementation with vitamin D may improve AD, but numbers very small from the meta-analysis
Serum vitamin D status in adult patients with atopic dermatitis: Recommendations for daily practice Study from University Medical Center Utrecht between 3/13-3/14 of adult atopic patients Divided as difficult to treat on immunosuppressives, or on topical steroids 210 total subjects JAAD Volume 75, Issue 6, Pages 1257-1259 (December 2016) DOI: 10.1016/j.jaad.2016.07.035
JAAD Volume 75, Issue 6, Pages 1257-1259 (December 2016) DOI: 10.1016/j.jaad.2016.07.035
Fig 1 Distribution of vitamin D status different by treatment status Patients with difficult to treat AD had increased proportion of vitamin D deficiency Check vitamin D status in our difficult to treat patients JAAD Volume 75, Issue 6, Pages 1257-1259 (December 2016) DOI: 10.1016/j.jaad.2016.07.035 Journal of the American Academy of Dermatology 2016 75, 1257-1259DOI: (10.1016/j.jaad.2016.07.035)
Mendelian randomization uses genetic associations to assess disease risks UK Biobank resource and from the SUNLIGHT(vitamin D), GABRIEL(asthma) and EAGLE (eczema) consortia. Identified 33,996 individuals strongly associated with 25-hydroxyvitamin D (25OHD) polymorphisms MR studies estimated the effect of lowered 25OHD on the risk of asthma (n = 146,761), childhood onset asthma (n = 15,008), atopic dermatitis (n = 40,835), and elevated IgE level (n = 12,853) and tested MR assumptions in sensitivity analyses PLoS Med. 2017 May 9;14(5):e1002294.
Conclusions for vitamin D and Atopic Dermatitis The controversy continues! Further studies still need to be performed to see if vitamin D can improve the manifestations of AD